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      Impact of nutritional index on the association between phosphorus concentrations and mortality in haemodialysis patients: a cohort study from dialysis outcomes and practice pattern study in Japan

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          Abstract

          Objectives

          While maintenance of both phosphorus concentration and nutritional status is a major concern in managing haemodialysis patients, the interaction between these parameters is not well understood. The aim of this study was to assess whether or not nutritional index influences the association between phosphorus concentration and all-cause mortality.

          Design

          A cohort study.

          Setting

          The Dialysis Outcomes and Practice Pattern Study, which included 99 representative dialysis facilities in Japan between 1997 and 2010.

          Participants

          A total of 6230 adult haemodialysis patients who had spent at least 6 months on haemodialysis.

          Main predictors

          Six categories based on time-averaged factors of the geriatric nutritional risk index (GNRI; the lowest two and highest tertiles) and phosphorus concentration (<3.5, 3.5 to <6 and ≥6 mg/dL).

          Primary outcome measure

          All-cause mortality rate.

          Analysis

          Time-dependent Cox regression adjusting for potential confounders.

          Results

          During the follow-up period (12 294 person-years), we noted 561 deaths (4.6 per 100 person-years), and both high phosphorus concentrations and low-middle GNRI were separately associated with all-cause mortality. The harmful effect of high phosphorus concentrations on all-cause mortality was stronger in patients with high GNRI than in those with low-middle GNRI. On the other hand, the harmful effect of low phosphorus concentrations was stronger in those with low-middle GNRI than in those with high GNRI. Relative excess risk due to interaction (RERI) between high phosphorus concentrations and low-middle GNRI was −0.57, indicating an antagonistic interaction. We also observed a significant statistical multiplicative interaction between phosphorus concentrations and GNRI (p=0.05 by likelihood ratio test).

          Conclusions

          The association between time-averaged serum phosphorus concentration and all-cause mortality differs across the nutritional index. Accordingly, nutritional index should be considered when the impact of phosphorus concentration on mortality in haemodialysis patients is evaluated.

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          Most cited references25

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          Geriatric Nutritional Risk Index: a new index for evaluating at-risk elderly medical patients.

          Patients at risk of malnutrition and related morbidity and mortality can be identified with the Nutritional Risk Index (NRI). However, this index remains limited for elderly patients because of difficulties in establishing their normal weight. Therefore, we replaced the usual weight in this formula by ideal weight according to the Lorentz formula (WLo), creating a new index called the Geriatric Nutritional Risk Index (GNRI). First, a prospective study enrolled 181 hospitalized elderly patients. Nutritional status [albumin, prealbumin, and body mass index (BMI)] and GNRI were assessed. GNRI correlated with a severity score taking into account complications (bedsores or infections) and 6-mo mortality. Second, the GNRI was measured prospectively in 2474 patients admitted to a geriatric rehabilitation care unit over a 3-y period. The severity score correlated with albumin and GNRI but not with BMI or weight:WLo. Risk of mortality (odds ratio) and risk of complications were, respectively, 29 (95% CI: 5.2, 161.4) and 4.4 (95% CI: 1.3, 14.9) for major nutrition-related risk (GNRI: <82), 6.6 (95% CI: 1.3, 33.0), 4.9 (95% CI: 1.9, 12.5) for moderate nutrition-related risk (GNRI: 82 to <92), and 5.6 (95% CI: 1.2, 26.6) and 3.3 (95% CI: 1.4, 8.0) for a low nutrition-related risk (GNRI: 92 to < or =98). Accordingly, 12.2%, 31.4%, 29.4%, and 27.0% of the 2474 patients had major, moderate, low, and no nutrition-related risk, respectively. GNRI is a simple and accurate tool for predicting the risk of morbidity and mortality in hospitalized elderly patients and should be recorded systematically on admission.
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            A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.

            Malnutrition inflammation complex syndrome (MICS) occurs commonly in maintenance hemodialysis (MHD) patients and may correlate with increased morbidity and mortality. An optimal, comprehensive, quantitative system that assesses MICS could be a useful measure of clinical status and may be a predictor of outcome in MHD patients. We therefore attempted to develop and validate such an instrument, comparing it with conventional measures of nutrition and inflammation, as well as prospective hospitalization and mortality. Using components of the conventional Subjective Global Assessment (SGA), a semiquantitative scale with three severity levels, the Dialysis Malnutrition Score (DMS), a fully quantitative scoring system consisting of 7 SGA components, with total score ranging between 7 (normal) and 35 (severely malnourished), was recently developed. To improve the DMS, we added three new elements to the 7 DMS components: body mass index, serum albumin level, and total iron-binding capacity to represent serum transferrin level. This new comprehensive Malnutrition-Inflammation Score (MIS) has 10 components, each with four levels of severity, from 0 (normal) to 3 (very severe). The sum of all 10 MIS components ranges from 0 to 30, denoting increasing degree of severity. These scores were compared with anthropometric measurements, near-infrared-measured body fat percentage, laboratory measures that included serum C-reactive protein (CRP), and 12-month prospective hospitalization and mortality rates. Eighty-three outpatients (44 men, 39 women; age, 59 +/- 15 years) on MHD therapy for at least 3 months (43 +/- 33 months) were evaluated at the beginning of this study and followed up for 1 year. The SGA, DMS, and MIS were assessed simultaneously on all patients by a trained physician. Case-mix-adjusted correlation coefficients for the MIS were significant for hospitalization days (r = 0.45; P < 0.001) and frequency of hospitalization (r = 0.46; P < 0.001). Compared with the SGA and DMS, most pertinent correlation coefficients were stronger with the MIS. The MIS, but not the SGA or DMS, correlated significantly with creatinine level, hematocrit, and CRP level. During the 12-month follow-up, 9 patients died and 6 patients left the cohort. The Cox proportional hazard-calculated relative risk for death for each 10-unit increase in the MIS was 10.43 (95% confidence interval, 2.28 to 47.64; P = 0.002). The MIS was superior to its components or different subversions for predicting mortality. The MIS appears to be a comprehensive scoring system with significant associations with prospective hospitalization and mortality, as well as measures of nutrition, inflammation, and anemia in MHD patients. The MIS may be superior to the conventional SGA and the DMS, as well as to individual laboratory values, as a predictor of dialysis outcome and an indicator of MICS.
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              Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy.

              Elevated calcium and phosphorus levels after therapy with injectable vitamin D for secondary hyperparathyroidism may accelerate vascular disease and hasten death in patients undergoing long-term hemodialysis. Paricalcitol, a new vitamin D analogue, appears to lessen the elevations in serum calcium and phosphorus levels, as compared with calcitriol, the standard form of injectable vitamin D. We conducted a historical cohort study to compare the 36-month survival rate among patients undergoing long-term hemodialysis who started to receive treatment with paricalcitol (29,021 patients) or calcitriol (38,378 patients) between 1999 and 2001. Crude and adjusted survival rates were calculated and stratified analyses were performed. A subgroup of 16,483 patients who switched regimens was also evaluated. The mortality rate among patients receiving paricalcitol was 3417 per 19,031 person-years (0.180 per person-year), as compared with 6805 per 30,471 person-years (0.223 per person-year) among those receiving calcitriol (P<0.001). The difference in survival was significant at 12 months and increased with time (P<0.001). In the adjusted analysis, the mortality rate was 16 percent lower (95 percent confidence interval, 10 to 21 percent) among paricalcitol-treated patients than among calcitriol-treated patients. A significant survival benefit was evident in 28 of 42 strata examined, and in no stratum was calcitriol favored. At 12 months, calcium and phosphorus levels had increased by 6.7 and 11.9 percent, respectively, in the paricalcitol group, as compared with 8.2 and 13.9 percent, respectively, in the calcitriol group (P<0.001). The two-year survival rate among patients who switched from calcitriol to paricalcitol was 73 percent, as compared with 64 percent among those who switched from paricalcitol to calcitriol (P=0.04). Patients who receive paricalcitol while undergoing long-term hemodialysis appear to have a significant survival advantage over those who receive calcitriol. A prospective, randomized study is critical to confirm these findings. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2017
                7 August 2017
                : 7
                : 8
                : e016682
                Affiliations
                [1 ] departmentDepartment of Healthcare Epidemiology , Graduate School of Medicine and Public Health, Kyoto University , Kyoto, Japan
                [2 ] Center for Innovative Research for Communities and Clinical Excellence (CIRC2LE), Fukushima Medical University , Fukushima, Japan
                [3 ] Institute for Health Outcomes and Process Evaluation Research (iHope International) , Kyoto, Japan
                [4 ] departmentDepartment of Medicine , Division of Nephrology, Showa University School of Medicine , Tokyo, Japan
                Author notes
                [Correspondence to ] Dr Shingo Fukuma; fukuma.shingo.3m@ 123456kyoto-u.ac.jp
                Article
                bmjopen-2017-016682
                10.1136/bmjopen-2017-016682
                5629681
                28790041
                25013d93-ef9c-4549-bb59-0c0d3252c89b
                © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 03 March 2017
                : 19 May 2017
                : 20 June 2017
                Categories
                Epidemiology
                Research
                1506
                1692
                1714
                Custom metadata
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                Medicine
                nephrology,epidemiology,dialysis
                Medicine
                nephrology, epidemiology, dialysis

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